Transcutaneous immunization with CD40 ligation boosts cytotoxic T lymphocyte mediated antitumor immunity independent of CD4 helper cells in mice

dc.contributor.authorBialojan, Ariane
dc.contributor.authorSohl, Julian
dc.contributor.authorRausch, Johanna
dc.contributor.authorAranda Lopez, Pamela
dc.contributor.authorDenny, Mark
dc.contributor.authorLangguth, Peter
dc.contributor.authorHartmann, Ann-Kathrin
dc.contributor.authorYagita, Hideo
dc.contributor.authorProbst, Hans Christian
dc.contributor.authorSchild, Hansjörg
dc.contributor.authorRadsak, Markus P.
dc.date.accessioned2022-06-20T10:31:22Z
dc.date.available2022-06-20T10:31:22Z
dc.date.issued2019
dc.description.abstractTranscutaneous immunization (TCI) is a novel vaccination strategy that utilizes skin-associated lymphatic tissue to induce immune responses. Employing T-cell epitopes and the TLR7 agonist imiquimod onto intact skin mounts strong primary, but limited memory CTL responses. To overcome this limitation, we developed a novel imiquimod-containing vaccination platform (IMI-Sol) rendering superior primary CD8+ and CD4+ T-cell responses. However, it has been unclear whether IMI-Sol per se is restricted in terms of memory formation and tumor protection. In our present work, we demonstrate that the combined administration of IMI-Sol and CD40 ligation unleashes fullblown specific T-cell responses in the priming and memory phase, strongly enhancing antitumor protection in mice. Interestingly, these effects were entirely CD4+ T cell independent, bypassing the necessity of helper T cells. Moreover, blockade of CD70 in vivo abrogated the boosting effect of CD40 ligation, indicating that the adjuvant effect of CD40 in TCI is mediated via CD70 on professional APCs. Furthermore, this work highlights the so far underappreciated importance of the CD70/CD27 interaction as a promising adjuvant target in TCI. Summing up, we demonstrate that the novel formulation IMI-Sol represents a powerful vaccination platform when applied in combination with sufficient adjuvant thereby overcoming current limitations of TCI.en_GB
dc.identifier.doihttp://doi.org/10.25358/openscience-7181
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7195
dc.language.isoengde
dc.rightsCC-BY-4.0*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleTranscutaneous immunization with CD40 ligation boosts cytotoxic T lymphocyte mediated antitumor immunity independent of CD4 helper cells in miceen_GB
dc.typeZeitschriftenaufsatzde
jgu.journal.issue11de
jgu.journal.titleEuropean journal of immunologyde
jgu.journal.volume49de
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.nameJohannes Gutenberg-Universität Mainz
jgu.organisation.number2700
jgu.organisation.placeMainz
jgu.organisation.rorhttps://ror.org/023b0x485
jgu.pages.end2094de
jgu.pages.start2083de
jgu.publisher.doi10.1002/eji.201848039de
jgu.publisher.issn1521-4141de
jgu.publisher.nameWiley-VCHde
jgu.publisher.placeWeinheimde
jgu.publisher.year2019
jgu.rights.accessrightsopenAccess
jgu.subject.ddccode610de
jgu.type.dinitypeArticleen_GB
jgu.type.resourceTextde
jgu.type.versionPublished versionde

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